Several human lymphoblastoid cell lines have been rendered persistently infected with measles virus by infecting at multiplicities of 1 PFU/10 to the sixth power cells. Seventy clones of virus have been obtained from these cell lines, and 50/70 are ts mutants. The mutants produced are heterogeneous, and by complementation analysis at least five and possibly six genes are affected in different isolates. A model for multiple sclerosis based on persistence of mutants in lymphoid cells and production of antigenic variants has been suggested. In addition, study of measles induced suppresor cells in MS patients relative to normals revealed a defect in measles antigen recognition such that few MS patients were able to suppress their own Con A response. The mechanism of the measles induced suppression of normal individuals was elucidated and shown to be mediated by interferon, indicating a defect in MS patients with respect to their ability to produce inteferon upon exposure to measles antigen. It was found that virus PI tumor cell lines were actively rejected by nude mice in vivo, and were killed in vitro by NK cells. The NK cells were activated by the persistently infected cell lines in vivo and by interferon in vitro. NK cells thus may have an important role to play in restricting persistent infections as well as in eliminating tumors expressing viruses.